Publications by authors named "Sayena Jabbehdari"

46 Publications

Higher prevalence of fundus haemorrhages in early-screened (NEST Study) as compared to late-screened (SUNDROP Study) newborn populations.

Br J Ophthalmol 2021 Jan 29. Epub 2021 Jan 29.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA

Background/aims: To determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4-11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.

Methods: Retrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.

Results: A total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.

Conclusion: We found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.
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http://dx.doi.org/10.1136/bjophthalmol-2020-317908DOI Listing
January 2021

Development of Choroidal Neovascularization after Treatment with Photodynamic Therapy in a 5-year old Female with Choroidal Osteoma.

Retin Cases Brief Rep 2020 Nov 17. Epub 2020 Nov 17.

Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois, USA.

Purpose: To describe a patient with a choroidal osteoma treated with PDT to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with PDT.

Methods: Case report.

Results: A 5-year-old Hispanic female presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical and family history was unremarkable. At examination, best corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. PDT was performed in order to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. CNV had been never reported in her past history as well as her follow up visits over seven years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported.

Conclusions: Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. PDT is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following PDT can be seen in the retina.
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http://dx.doi.org/10.1097/ICB.0000000000001089DOI Listing
November 2020

Effect of dietary modification and antioxidant supplementation on intraocular pressure and open-angle glaucoma.

Eur J Ophthalmol 2020 Oct 2:1120672120960337. Epub 2020 Oct 2.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.

Primary open-angle glaucoma (POAG) is an age-dependent, intraocular pressure (IOP)-related degeneration of the retinal ganglion cells (RGC). At present, IOP is the only modifiable factor that has been identified to prevent glaucomatous vision loss. Though the pathogenesis of glaucomatous optic neuropathy is still not well understood, increasing evidence suggests oxidative stress may contribute to the induction and progression of glaucoma. Furthermore, antioxidant use may be protective against glaucoma through various mechanisms, including reducing IOP, preserving vascular health, and preventing ganglion cell loss. This article provides a comprehensive review of the effect of oxidative stress, diet, and antioxidant therapy on IOP and open-angle glaucoma.
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http://dx.doi.org/10.1177/1120672120960337DOI Listing
October 2020

Oxidative stress as a therapeutic target for the prevention and treatment of early age-related macular degeneration.

Surv Ophthalmol 2020 Sep 19. Epub 2020 Sep 19.

Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. Electronic address:

Age-related macular degeneration, the leading cause of irreversible visual loss among older adults in developed countries, is a chronic, multifactorial, and progressive disease with the development of painless, central vision loss. Retinal pigment epithelial cell dysfunction is a core change in age-related macular degeneration that results from aging and the accumulated effects of genetic and environmental factors that, in part, is both caused by and leads to oxidative stress. In this review, we describe the role of oxidative stress, the cytoprotective oxidative stress pathways, and the impact of oxidative stress on critical cellular processes involved in age-related macular degeneration pathobiology. We also offer targeted therapy that may define how antioxidant therapy can either prevent or improve specific stages of age-related macular degeneration.
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http://dx.doi.org/10.1016/j.survophthal.2020.09.002DOI Listing
September 2020

Developmental distribution of primary cilia in the retinofugal visual pathway.

J Comp Neurol 2020 Sep 17. Epub 2020 Sep 17.

Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA.

The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), bridge retinal input and visual output. The primary cilium is a conserved organelle increasingly viewed as a critical sensor for the regulation of developmental and homeostatic pathways in most mammalian cell types. Moreover, cilia have been described as crucial for neurogenesis, neuronal maturation, and survival in the cortex and retina. However, cilia in the visual relay center remain to be fully described. In this study, we characterized the ciliation profile of the SC and dLGN and found that the overall number of ciliated cells declined during development. Interestingly, shorter ciliated cells in both regions were identified as neurons, whose numbers remained stable over time, suggesting that cilia retention is a critical feature for optimal neuronal function in SC and dLGN. Our study suggests that primary cilia are important for neuronal maturation and function in cells of the SC and dLGN.
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http://dx.doi.org/10.1002/cne.25029DOI Listing
September 2020

Reproducible Derivation and Expansion of Corneal Mesenchymal Stromal Cells for Therapeutic Applications.

Transl Vis Sci Technol 2020 02 21;9(3):26. Epub 2020 Feb 21.

Stem Cell Therapy and Corneal Tissue Engineering Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: A reproducible protocol for the production of corneal mesenchymal stem/stromal cells (cMSCs) is necessary for potential clinical applications. We aimed to describe successful generation and expansion of cMSCs using an explant method.

Methods: Corneoscleral rims of human cadaveric eyes were divided into four pieces and used as explants to allow outgrowth of cMSCs (passage 0, or P0). The cells were subcultured at a 1:10 ratio until passage 5 (P5). The characteristics as well as therapeutic effects of expanded cMSCs were evaluated both in vitro, using a scratch assay, and in vivo using epithelial debridement and chemical injury mouse models.

Results: All explants demonstrated outgrowth of cells by 7 days. Although the initial outgrowth included mixed mesenchymal and epithelial cells, by P1 only cMSCs remained. By subculturing each flask at a ratio of 1:10, the potential yield from each cornea was approximately 12 to 16 × 10 P5 cells. P5 cMSCs demonstrated the cell surface markers of MSCs. The secretome of P5 cMSCs induced faster closure of wounds in an in vitro scratch assay. Subconjunctival injection of P5 cMSCs in mouse models of mechanical corneal epithelial debridement or ethanol injury led to significantly faster wound healing and decreased inflammation, relative to control.

Conclusions: cMSCs can be reproducibly derived from human cadaveric corneas using an explant method and expanded with preservation of characteristics and corneal wound healing effects.

Translational Relevance: The results of our study showed that cMSCs produced using this scheme can be potentially used for clinical applications.
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http://dx.doi.org/10.1167/tvst.9.3.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354855PMC
February 2020

The Effect of Mesenchymal Stem Cell Secretome on Corneal Endothelial Cell Preservation in an Oxidative Injury Model.

Cornea 2020 Nov;39(11):1426-1430

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL; and.

Purpose: To describe a reproducible oxidative injury model in ex vivo porcine corneas and to investigate the effects of corneal mesenchymal stem cell (Co-MSC) secretome and specific factors on the preservation of corneal endothelium after oxidative injury.

Methods: Porcine corneas underwent vital staining with trypan blue and alizarin red with different concentration and time points. Ex vivo porcine corneas were exposed (endothelial side) to varied concentrations of hydrogen peroxide. After injury, 3 groups of 5 corneas underwent treatment with secretome from either a wild-type (WT) murine Co-MSC, a pigment epithelium derived factor (PEDF) knock out (K/O) murine Co-MSC, or basal media for 4 hours at 37°C. The viability of the endothelium was evaluated using the optimized vital staining protocol.

Results: The optimal vital staining was achieved with 0.4% trypan blue for 60 seconds and 0.5% alizarin red for 90 seconds. The optimal oxidative injury (for consistency and level of damage) was obtained with 1% hydrogen peroxide for 15 seconds. Treatment with both WT Co-MSC and PEDF K/O Co-MSC secretome significantly reduced the endothelial damage compared with control (17.2% ± 10.0%, 33.5% ± 11.6%, and 68% ± 17%, respectively, P < 0.01). The WT Co-MSC secretome was significantly more effective compared with PEDF K/O Co-MSC secretome (P < 0.05).

Conclusions: A reproducible model of vital staining and oxidative injury is described for studying porcine corneal endothelial survival. Our results demonstrate a beneficial role of a corneal MSC secretome in reducing oxidative damage to the corneal endothelium. In addition, it suggests a potential role for PEDF in this process.
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http://dx.doi.org/10.1097/ICO.0000000000002442DOI Listing
November 2020

Update on the pathogenesis and management of ocular rosacea: an interdisciplinary review.

Eur J Ophthalmol 2021 Jan 25;31(1):22-33. Epub 2020 Jun 25.

Department of Ophthalmology, University of Illinois at Chicago, Chicago, IL, USA.

Purpose: Rosacea is one of the most common conditions affecting the ocular surface. The purpose of this review is to provide an update on the pathogenesis and treatment of rosacea based on the dermatology and ophthalmology literatures.

Methods: Literature searches were conducted for rosacea and ocular rosacea. Preference was given to systematic reviews, meta-analysis, case-controlled studies, and documented case reports while excluding poorly documented case studies and commentaries. The data were examined and independently analyzed by more than two of the authors.

Results: Rosacea is a complex inflammatory condition involving the pilosebaceous unit. Its underlying mechanism involves an interplay of the microbiome, innate immunity, adaptive immunity, environmental triggers, and neurovascular sensitivity. The latest classification of rosacea includes three dermatologic subgroups and a fourth subgroup, ocular rosacea. Ocular rosacea clinically displays many features that are analogous to the cutaneous disease, such as lid margin telangiectasia and phlyctenulosis. The role of environmental triggers in the exacerbation of ocular rosacea appears to be understudied. While lid hygiene and systemic treatment with tetracycline drugs remain the mainstay of treatment for ocular rosacea, newer dermatologic targets and therapies may have potential application for the eye disease.

Conclusions: Ocular rosacea appears to embody many of the manifestation of the dermatologic disease. Hence, the basic pathophysiologic mechanisms of the ocular and cutaneous disease are likely to be shared. Better understanding of the ocular surface microbiome and the immunologic mechanisms, may lead to novel approaches in the management of ocular rosacea.
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http://dx.doi.org/10.1177/1120672120937252DOI Listing
January 2021

Bilateral focal choroidal excavations in a patient with Stargardt disease and ocular toxoplasmosis.

Eur J Ophthalmol 2020 Jun 3:1120672120932092. Epub 2020 Jun 3.

Horngren Family Vitreoretinal Center, Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA.

Introduction: Focal choroidal excavation (FCE) is a concavity of the choroid detected on optical coherence tomography (OCT). It is usually idiopathic and the affected eyes are otherwise healthy with near-normal overlying retinal architecture and good visual acuity.

Purpose: To report a case of bilateral conforming FCE in the setting of Stargardt disease and inactive ocular toxoplasmosis.

Case Report: A 20-year-old man with known history of Stargardt disease, healed toxoplasmosis, and high myopia presented to our ophthalmology department for follow-up examination and was found with bilateral FCEs not present in any of his previous examinations.

Conclusion: FCEs have been reported in the literature in otherwise healthy eyes as well as a broad spectrum of ocular diseases. The case herein reported Stargardt disease, toxoplasmosis, and high myopia all could potentially contribute to the pathogenesis of these findings. Further studies are needed to define etiologies as well as clinical significance and course of FCEs.
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http://dx.doi.org/10.1177/1120672120932092DOI Listing
June 2020

Oculocerebrorenal syndrome of Lowe: Survey of ophthalmic presentations and management.

Eur J Ophthalmol 2020 Sep 27;30(5):966-973. Epub 2020 Apr 27.

Department of Ophthalmology, School of Medicine, Stanford University, Palo Alto, CA, USA.

Background: Lowe syndrome is a rare X-linked disease that is characterized by renal dysfunction, developmental delays, congenital cataracts and glaucoma. Mutations in the oculocerebral renal syndrome of Lowe () gene are found in Lowe syndrome patients. Although loss of vision is a major concern for families and physicians who take care of Lowe syndrome children, definitive cause of visual loss is still unclear. Children usually present with bilateral dense cataracts at birth and glaucoma, which occurs in more than half of cases, either concurrently or following cataract surgery.

Materials And Methods: A retrospective review was conducted on the prevalence and characteristics of ocular findings among families of patients with Lowe syndrome with 137 uniquely affected individuals.

Results: Of 137 patients, all had bilateral congenital cataracts. Nystagmus was reported in 69.3% of cases, glaucoma in 54.7%, strabismus in 35.0%, and corneal scar in 18.2% of patients. Glaucoma was reported as the most common cause of blindness (46%) followed by corneal scars (41%). Glaucoma occurred in 54.7% of patients and affected both eyes in the majority of cases. Of these patients, 55% underwent surgery for glaucoma, while the remaining patients used medications to control their eye pressure. Timolol and latanoprost were the most commonly used medications. Although trabeculectomy and goniotomy are commonly used for pressure management, aqueous tube shunts had the best outcomes.

Conclusion: Ocular manifestations in individuals with Lowe syndrome and carriers with mutation are reported which may help familiarize clinicians with the ocular manifestations and management of a rare and complex syndrome.
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http://dx.doi.org/10.1177/1120672120920544DOI Listing
September 2020

Therapeutic Effects of Lyophilized Conditioned-Medium Derived from Corneal Mesenchymal Stromal Cells on Corneal Epithelial Wound Healing.

Curr Eye Res 2020 12 14;45(12):1490-1496. Epub 2020 May 14.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago , Chicago, Illinois, USA.

: The conditioned-medium derived from corneal mesenchymal stromal cells (cMSCs) has been shown to have wound healing and immunomodulatory effects in corneal injury models. Here, the therapeutic effects of lyophilized cMSC conditioned-medium were compared with fresh conditioned-medium. : The epithelial wound healing effects of fresh and lyophilized cMSC conditioned-medium were compared with conditioned-medium from non-MSC cells (corneal epithelial cells) using scratch assay. To evaluate the anti-inflammatory effects of fresh and lyophilized cMSC conditioned-media, macrophages were stimulated by a Toll-Like Receptor (TLR) ligand followed by treatment with the conditioned-media and measuring the expression of inflammatory genes. wound healing effects of fresh and lyophilized cMSC conditioned-media were assessed in a murine model of cornea epithelial injury. : Both fresh and lyophilized cMSCs-derived conditioned-medium induced significantly faster closure of in vitro epithelial wounds compared to conditioned-medium from non-MSC cells ( < .0001). Treating stimulated macrophages with fresh or lyophilized cMSCs-derived conditioned-media significantly decreased the expression of inflammatory genes compared to control ( < .0001). Murine corneal epithelial wounds were healed by 87.6 ± 2.7% and 86.2 ± 4.6% following treatment with fresh and lyophilized cMSC conditioned-media, respectively, while the control was healed by 64.7 ± 16.8% ( < .05). : Lyophilized cMSC-derived conditioned-medium is as effective as fresh conditioned-medium in promoting wound healing and modulating inflammation. The results of this study support the application of lyophilized cMSCs-derived conditioned-medium, which allows for more extended storage, as a promising non-invasive option in the treatment of corneal wounds.
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http://dx.doi.org/10.1080/02713683.2020.1762227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666083PMC
December 2020

The Role of Multisystem Disease in Composition of Autologous Serum tears and ocular surface symptom improvement.

Ocul Surf 2020 07 29;18(3):499-504. Epub 2020 Feb 29.

Ophthalmology, Loyola University Medical Center, Maywood, IL, USA. Electronic address:

Purpose: Autologous serum tears (AST) contain growth factors and vitamins similar to those in healthy tears and are an effective treatment option for ocular surface disease. This study determined the differences in composition of AST in patients with systemic diseases versus patients with localized ocular surface diseases and the effects on ocular surface symptom improvement.

Method: An observational study was performed on 53 patients with either systemic diseases (Group I) or localized ocular surface diseases (Group II) who were prescribed AST. Concentrations of epidermal growth factor (EGF), interleukin 8 (IL-8), fibronectin, vitamin A, and tumor necrosis factor-α (TNF-α) were determined through ELISA assays from patients in both groups. The Ocular Surface Disease Index (OSDI) scores were calculated prior to and 6 weeks after initiation of treatment with AST for new patients.

Results: The average concentration of EGF in Group I (29.39 pg/ml ± 52.85 pg/ml) was significantly lower than in Group II (88.04 pg/ml ±113.75 pg/ml) (p < 0.05). Levels of fibronectin, IL-8, and vitamin A were similar in both groups. There was a 24% reduction in OSDI score 6 weeks after initiation in Group I compared to a 36% reduction reported in Group II (p = 0.065). The OSDI score was reduced significantly after the treatment in all subjects (p = 0.002).

Conclusion: Serum tears are a promising therapy for management of ocular surface disease and associated symptoms. The differences between levels of EGF in patients with localized ocular surface disease and systemic inflammatory disease may account for differences in therapeutic outcome.
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http://dx.doi.org/10.1016/j.jtos.2020.02.011DOI Listing
July 2020

Application of Hemifield Visual Electrophysiology to Diagnose Functional Vision Loss.

J Neuroophthalmol 2020 12;40(4):527-529

Departments of Ophthalmology (HEM), and Neurology and Neurological Sciences (HEM), Stanford University, Palo Alto, California; and Department of Ophthalmology and Visual Sciences (SJ), University of Illinois at Chicago, Chicago, Illinois.

Neuro-ophthalmologists frequently see patients who are experiencing vision loss not accounted for by a neuro-ophthalmic disorder. In this article, we describe a case of binasal hemianopia in an otherwise healthy 65-year-old woman who was initially diagnosed with glaucoma but ultimately proved to have functional visual loss. This diagnosis was made by confirming by confirming normal visual pathway function using hemifield visual-evoked potential studies.
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http://dx.doi.org/10.1097/WNO.0000000000000882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737647PMC
December 2020

Dexamethasone 0.4mg Sustained-Release Intracanalicular Insert in the Management of Ocular Inflammation and Pain Following Ophthalmic Surgery: Design, Development and Place in Therapy.

Clin Ophthalmol 2020 13;14:89-94. Epub 2020 Jan 13.

Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA.

Inflammation and pain are two prevalent findings after ocular surgery. Corticosteroids are widely administrated as a core treatment to control post-surgical inflammation and pain. Improper patient adherence to post-operative eye drop regimens, limited bioavailability of topical eye drops, and the negative impact of preservatives used in many of these eye drops, has made a strong case for novel therapies in the treatment of post-operative pain and inflammation. This review of the literature will focus on the role of intracanalicular sustained-release dexamethasone (Dextenza, Ocular Therapeutix, Bedford, MA, USA) for the management of ocular inflammation and pain.
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http://dx.doi.org/10.2147/OPTH.S238756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968807PMC
January 2020

Anterior Optic Neuropathy in a Patient With Cyclical Fevers.

JAMA Ophthalmol 2020 03;138(3):314-315

Department of Ophthalmology, Stanford University, Palo Alto, California.

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http://dx.doi.org/10.1001/jamaophthalmol.2019.4987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713502PMC
March 2020

Colour change in the newborn iris: 2-year follow-up of the Newborn Eye Screening Test study.

Acta Ophthalmol 2020 Jun 6;98(4):e521-e522. Epub 2019 Dec 6.

Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, USA.

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http://dx.doi.org/10.1111/aos.14321DOI Listing
June 2020

Ocular surface involvement in pemphigus vulgaris: An interdisciplinary review.

Ocul Surf 2020 01 12;18(1):40-46. Epub 2019 Oct 12.

Department of Ophthalmology, University of Illinois Health Hospital System, Chicago, IL, USA.

Purpose: A review of the published literature on the history, pathogenesis, and treatment of pemphigus vulgaris (PV) and its ocular involvement.

Methods: Literature searches were conducted in MEDLINE (Ovid), and google scholar for pemphigus vulgaris and ocular PV. Inclusion criteria were given to meta-analysis, case-controlled studies, and documented case reports. The data were examined and independently analyzed by more than two of the authors.

Results: PV is a humoral autoimmune disease with a preponderance of IgG4 anti-desmoglein 3 antibodies. Upon antibody binding, there is an intracellular signaling mechanism that leads to blister formation. Ocular findings are seen in up to 16% of PV patients with conjunctivitis being the most common clinical presentation. New steroid-sparing agents have helped with the control of this deadly disease, and with better understanding of the pathogenesis of PV, other cytokine blockers currently available are promising steroid-sparing agents.

Conclusions: Ocular pemphigus can occasionally present prior to mucocutaneous findings. Recalcitrant conjunctivitis with conjunctival blisters should warrant a workup for systemic PV.
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http://dx.doi.org/10.1016/j.jtos.2019.09.008DOI Listing
January 2020

Regression of corneal neovascularization: Adiponectin versus bevacizumab eye drops.

Eur J Ophthalmol 2021 Jan 15;31(1):78-82. Epub 2019 Sep 15.

School of Civil Engineering, College of Engineering, University of Tehran, Tehran, Iran.

Purpose: Comparing the effect of adiponectin versus bevacizumab in decreasing corneal neovascularization.

Methods: This study was conducted on 30 eyes of 30 New Zealand Albino male rabbits. Corneal neovascularization was induced by a single 7-0 silk suture 2 mm long and 1 mm in front of the limbus for 2 weeks. Rabbits were randomly divided into three groups of adiponectin (20 µg/mL), bevacizumab (5 mg/mL) and artificial tears. The treatments continued up to 14 days.

Results: At the end of 14 days, the average length of vessels in rabbits treated with adiponectin, bevacizumab and control groups decreased from 2.12 ± 0.32 mm to 0.89 ± 0.46 mm (57.68% ± 19.98%) (P < 0.001), 2.30 ± 0.41 mm to 1.30 ± 0.58 mm (42.49% ± 27.17%) (P = 0.048) and from 2.12 ± 0.44 mm to 1.81 ± 0.42 mm (14.81% ± 5.64%) (P = 0.112), respectively. The length of vessels decreased 57.68% ± 19.98% and 42.49% ± 27.17% in adiponectin versus bevacizumab groups, respectively (P = 0.527). The average surface area of vessels in rabbits treated with adiponectin, bevacizumab and control groups reduced from 5.02 ± 1.50 mm to 1.40 ± 0.75 mm (70.64% ± 17.76%) (P < 0.001) 0.34 ± 1.1 mm to 2.80 ± 1.04 mm (48.24% ± 19.23%) (P = 0.039) and 5.12 ± 2.92 mm to 4.4 ± 2.55 mm (14.68% ± 4.19%) (P = 0.117). Mean surface area of vascularization decreased 70.64% ± 17.76% and 48.24% ± 19.23% in adiponectin versus bevacizumab, respectively (P = 0.013).

Conclusions: The results of this study suggest that topical adiponectin can decrease recent corneal neovascularization.
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http://dx.doi.org/10.1177/1120672119874947DOI Listing
January 2021

Emerging Approaches for Ocular Surface Regeneration.

Curr Ophthalmol Rep 2019 Mar 17;7(1):1-10. Epub 2019 Jan 17.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.

Purpose Of Review: In this manuscript, the recent advancements and novel approaches for regeneration of the ocular surface are summarized.

Recent Findings: Following severe injuries, persistent inflammation can alter the rehabilitative capability of the ocular surface environment. Limbal stem cell deficiency (LSCD) is one of the most characterized ocular surface disorders mediated by deficiency and/or dysfunction of the limbal epithelial stem cells (LESCs) located in the limbal niche. Currently, the most advanced approach for revitalizing the ocular surface and limbal niche is based on transplantation of limbal tissues harboring LESCs. Emerging approaches have focused on restoring the ocular surface microenvironment using (1) cell-based therapies including cells with capabilities to support the LESCs and modulate the inflammation, e.g., mesenchymal stem cells (MSCs), (2) bio-active extracellular matrices from decellularized tissues, and/or purified/synthetic molecules to regenerate the microenvironment structure, and (3) soluble cytokine/growth factor cocktails to revive the signaling pathways.

Summary: Ocular surface/limbal environment revitalization provide promising approaches for regeneration of the ocular surface.
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http://dx.doi.org/10.1007/s40135-019-00193-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605053PMC
March 2019

The importance of early diagnosis of Stickler syndrome: Finding opportunities for preventing blindness.

Taiwan J Ophthalmol 2018 Oct-Dec;8(4):189-195

Retina Consultants Ltd., Des Plaines, Illinois, USA.

Stickler Syndrome (SS) is a significant cause of retinal blindness in children. The immediate cause of blindness is retina detachment from giant retinal tear (GRT). It is frequently diagnosed late and the giant retinal tear (GRT) may be complicated by high-grade proliferative vitreoretinopathy (PVR). The surgery for the combined GRT with PVR has limited structural results and the vision mainly remains impaired. In order to improve the visual outcomes, we propose an organized program oriented toward early diagnosis and surveillance. Adding an effective prophylaxis may maintain normal vision in a high percent of patients. The critical diagnostic moments for this program are prenatal and at birth. The tools include a directed history, general physical exam and advanced ophthalmologic exam looking for the particular features of SS. Some features may need advanced skills transfer, because they are not reliably taught in retina fellowships. Much of this program requires a partnership with obstetricians, pediatricians, neonatologists and geneticists. Finally, we review the evidence regarding prophylaxis and discuss our approach in the absence of guidance from a randomized clinical trial.
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http://dx.doi.org/10.4103/tjo.tjo_97_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302565PMC
January 2019

Strategies for reconstructing the limbal stem cell niche.

Ocul Surf 2019 04 8;17(2):230-240. Epub 2019 Jan 8.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA. Electronic address:

The epithelial cell layer that covers the surface of the cornea provides a protective barrier while maintaining corneal transparency. The rapid and effective turnover of these epithelial cells depends, in part, on the limbal epithelial stem cells (LESCs) located in a specialized microenvironment known as the limbal niche. Many disorders affecting the regeneration of the corneal epithelium are related to deficiency and/or dysfunction of LESCs and the limbal niche. Current approaches for regenerating the corneal epithelium following significant injuries such as burns and inflammatory attacks are primarily aimed at repopulating the LESCs. This review summarizes and assesses the clinical feasibility and efficacy of current and emerging approaches for reconstruction of the limbal niche. In particular, the application of mesenchymal stem cells along with appropriate biological scaffolds appear to be promising strategies for long-term revitalization of the limbal niche.
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http://dx.doi.org/10.1016/j.jtos.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529262PMC
April 2019

Management of advanced ocular surface disease in patients with severe atopic keratoconjunctivitis.

Ocul Surf 2019 04 4;17(2):303-309. Epub 2018 Dec 4.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA. Electronic address:

Aim & Objective: Severe ocular surface disease, including limbal stem cell deficiency (LSCD) can occur as a consequence of severe atopic keratoconjunctivitis (AKC) that has been inadequately treated. Our goal was to describe the management and outcomes of severe ocular surface disease in AKC patients.

Methods: We performed a retrospective analysis of a case series of 13 eyes of 8 patients with advanced ocular surface disease associated with severe AKC. The clinical presentation, medical and surgical management, and visual and anatomic outcomes were analyzed.

Results: Five eyes were treated with medical interventions alone, which included topical or systemic immunomodulatory therapy (IMT) for all eyes. These eyes had a decline in mean visual acuity from LogMAR 0.96 to 2.04 between the initial and final visits related to recurrent epithelial defects or corneal ulceration. Eight eyes were treated with surgical approaches in addition to medical treatment. Initial surgical treatments included limbal stem cell transplantation (n = 5), Boston keratoprosthesis (n = 2), and superficial keratectomy (n = 1). Both eyes that underwent primary keratoprosthesis had severe post-operative complications and became no light perception. In the remainder of the surgically treated eyes, there was an improvement visual acuity from LogMAR 1.43 to 0.6 between the pre-operative and final post-operative visit.

Conclusion: Visual rehabilitation in eyes severe ocular surface disease due to prolonged AKC is challenging. While some patients did experience improved vision, most eyes did not improve or experienced severe complications with vision loss. Early intervention with immunomodulatory therapy may prevent progression of the disease to advanced stages.
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http://dx.doi.org/10.1016/j.jtos.2018.12.002DOI Listing
April 2019

Current and emerging therapies for corneal neovascularization.

Ocul Surf 2018 10 20;16(4):398-414. Epub 2018 Jun 20.

Cincinnati Eye Institute, Edgewood, KY/ University of Cincinnati, Department of Ophthalmology, Cincinnati, OH, USA. Electronic address:

The cornea is unique because of its complete avascularity. Corneal neovascularization (CNV) can result from a variety of etiologies including contact lens wear; corneal infections; and ocular surface diseases due to inflammation, chemical injury, and limbal stem cell deficiency. Management is focused primarily on the etiology and pathophysiology causing the CNV and involves medical and surgical options. Because inflammation is a key factor in the pathophysiology of CNV, corticosteroids and other anti-inflammatory medications remain the mainstay of treatment. Anti-VEGF therapies are gaining popularity to prevent CNV in a number of etiologies. Surgical options including vessel occlusion and ocular surface reconstruction are other options depending on etiology and response to medical therapy. Future therapies should provide more effective treatment options for the management of CNV.
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http://dx.doi.org/10.1016/j.jtos.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461401PMC
October 2018

Ophthalmologic Findings in Patients with Neuro-metabolic Disorders.

J Ophthalmic Vis Res 2018 Jan-Mar;13(1):34-38

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.

Purpose: We aimed to present the ophthalmic manifestations of neuro-metabolic disorders.

Methods: Patients who were diagnosed with neuro-metabolic disorders in the Neurology Department of Mofid Pediatric Hospital in Tehran, Iran, between 2004 and 2014 were included in this study. Disorders were confirmed using clinical findings, neuroimaging, laboratory data, and genomic analyses. All enrolled patients were assessed for ophthalmological abnormalities.

Results: A total of 213 patients with 34 different neuro-metabolic disorders were included. Ophthalmological abnormalities were observed in 33.5% of patients. Abnormal findings in the anterior segment included Kayser-Fleischer rings, congenital or secondary cataracts, and lens dislocation into the anterior chamber. Posterior segment (i.e., retina, vitreous body, and optic nerve) evaluation revealed retinitis pigmentosa, cherry-red spots, and optic atrophy. In addition, strabismus, nystagmus, and lack of fixation were noted during external examination.

Conclusion: Ophthalmological examination and assessment is essential in patients that may exhibit neuro-metabolic disorders.
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http://dx.doi.org/10.4103/jovr.jovr_242_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782454PMC
February 2018

The role of amniotic membrane extract eye drop (AMEED) in in vivo cultivation of limbal stem cells.

Ocul Surf 2018 01 8;16(1):146-153. Epub 2017 Nov 8.

Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Background: Limbal stem cell transplantation (LSCT) is the definitive treatment for total limbal stem cell deficiency (LSCD). This study evaluates the anatomical and visual outcomes of a surgical technique supplemented by amniotic membrane extract eye drop (AMEED) for in vivo cultivation of limbal stem cells (LSCs).

Methods: One small limbal block (2 × 1 mm) harvested from the contralateral healthy eye was transferred to the diseased eye, which had been already covered by cryopreserved amniotic membrane (N = 20). The patients were categorized into case and control groups. AMEED was administered postoperatively only for patients in the case group (N = 14). Sequential penetrating keratoplasty (PKP) was performed in 4 eyes of the case group for optical clarity. Visual acuity, epithelial healing, corneal clarity and regression of conjunctivalization/vascularization were evaluated after surgery. The corneal buttons of post-PKP eyes were evaluated for LSC markers.

Results: In the case group, the mean corrected distance visual acuity (CDVA) was 20/400 before surgery, which improved to 20/40 and 20/50 at the last follow-up in eyes with and without PKP, respectively. Epithelial defects healed in all eyes of the case group during 2 weeks after surgery. Corneal conjunctivalization/vascularization regressed dramatically in all patients of the case group 2-3 months after surgery. In PKP cases, all transplanted corneas were clear at the last follow-up. LSC markers were expressed on the surface of all trephined corneal buttons. All eyes in the control group developed persistent epithelial defect.

Conclusion: This study suggests that amniotic membrane extract may be helpful for in vivo cultivation of limbal stem cells.
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http://dx.doi.org/10.1016/j.jtos.2017.11.001DOI Listing
January 2018

Unrestricted somatic stem cells, as a novel feeder layer: Ex vivo culture of human limbal stem cells.

J Cell Biochem 2018 03 30;119(3):2666-2678. Epub 2017 Nov 30.

Ocular Tissue Engineering Research Center, Shahid Beheshti University of medical sciences, Tehran, Iran.

Ex vivo culture of limbal stem cells (LSCs) is a current promising approach for reconstruction of the ocular surface. In this context, 3T3 feeder layer cells (mouse embryo fibroblast) are generally utilized to maintain and expand LSCs. The aim of this study is to develop a novel culture method (animal-derived products free) to expand LSCs, using umbilical cord derived human unrestricted somatic stem cells (hUSSCs) instead of 3T3 cell with an emphasis on maintaining of the Stemness in LSCs. Using flow-cytometer, isolated hUSSCs were characterized for CD105, CD90, CD166, CD34, CD45, CD31 cell surface markers and their differentiation capability into adipogenic as well as osteogenic lineages were evaluated. In addition to colony-forming efficiency (CFE), epithelial lineage differentiation and karyotyping, LSC properties were evaluated for ABCG2, ΔNP63-α, CK19, CK3, and CK12 mRNA and protein expressions using quantitative RT-PCR (qRT-PCR) and immunocytochemistry, when these cells were co-cultured with hUSSCs (in comparison with 3T3 feeder layer). LSCs, co-cultured with hUSSCs, showed normal karyotype (46, XX), while they could efficiently form colony (86 ± 3) and display up-regulation of the genes associated with stemness and down-regulation of corneal epithelial differentiation genes. Consistent with 3T3 feeder cells, hUSSCs with spindle-shaped morphology and quick splitting up properties had ability to preserve the stem like-cell phenotype of LSCs. These findings were confirmed by qRT-PCR and flow-cytometer. Findings of present study suggest hUSSCs as a promising alternative method for 3T3 feeder layer cells, to preserve growth and stemness of LSCs ex vivo culture.
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http://dx.doi.org/10.1002/jcb.26434DOI Listing
March 2018

Update on the Management of High-Risk Penetrating Keratoplasty.

Curr Ophthalmol Rep 2017 Mar 2;5(1):38-48. Epub 2017 Feb 2.

Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL.

Purpose Of Review: In this article, we review the indications and latest management of high-risk penetrating keratoplasty.

Recent Findings: Despite the immune-privilege status of the cornea, immune-mediated graft rejection still remains the leading cause of corneal graft failure. This is particularly a problem in the high-risk graft recipients, namely patients with previous graft failure due to rejection and those with inflamed and vascularized corneal beds. A number of strategies including both local and systemic immunosuppression are currently used to increase the success rate of high-risk corneal grafts. Moreover, in cases of limbal stem cell deficiency, limbal stem cells transplantation is employed.

Summary: Corticosteroids are still the top medication for prevention and treatment in cases of corneal graft rejection. Single and combined administration of immunosuppressive agents e.g. tacrolimus, cyclosporine and mycophenolate are promising adjunctive therapies for prolonging graft survival. In the future, cellular and molecular therapies should allow us to achieve immunologic tolerance even in high-risk grafts.
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http://dx.doi.org/10.1007/s40135-017-0119-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5612422PMC
March 2017

Pulmonary Actinomycosis in a Patient with AIDS/HCV.

J Clin Diagn Res 2017 Jun 1;11(6):OD15-OD17. Epub 2017 Jun 1.

Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis, Tehran, Iran.

Pulmonary actinomycosis is a rare bacterial lung infection which is caused mainly by Actinomyces israelii. This non contagious infection can destroy parts of the lungs. There are variable presentations of pulmonary actinomycosis with similarity in manifestations to other infectious diseases of the lungs. Pulmonary actinomycosis is diagnosed by fine needle aspiration, bronchoscopy and finding of typical sulfur granules. We present a case of pulmonary actinomycosis in a middle aged (AIDS/HCV) man with massive hemoptysis and progressive dyspnoea. The bronchoscopy findings showed endobronchial mass with luminal occlusion in right upper lobe. Because of massive hemoptysis and poor response to conservative treatment and penicillin therapy, right upper lobectomy was needed to stop the bleeding. Histopathologic examination revealed the aggregations of filamentous Gram-positive organisms with characteristic pattern "sulfur granules", indicating actinomycosis. The patient was followed by six months of oral amoxicillin and has no recurrent hemoptysis.
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http://dx.doi.org/10.7860/JCDR/2017/27593.10092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535422PMC
June 2017

Distribution scheme of antituberculosis drug resistance among HIV patients in a referral centre over 10 years.

J Glob Antimicrob Resist 2017 12 21;11:116-119. Epub 2017 Jul 21.

Clinical Tuberculosis and Epidemiology Research Center (CTERC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objectives: Antituberculosis drug resistance is increasing among tuberculosis (TB) patients globally, particularly in those who are human immunodeficiency virus (HIV)-positive. The aim of this study was to determine the pattern of anti-TB drug resistance in these patients in an effort to improve successful treatment outcomes with a proper regimen.

Methods: A cross-sectional study was conducted on adult TB/HIV co-infected patients from 2005-2015. The pattern of anti-TB drug resistance was evaluated among HIV-positive patients with and without a history of TB treatment. Categorisation was made as follows: isoniazid (INH)-resistant; rifampicin (RIF)-resistant; or multidrug-resistant (MDR).

Results: A total of 52 patients were enrolled in this study (median age 38 years). Among the 52 patients, 18 (34.6%) were MDR-TB patients and the rest were monoresistant TB (resistant either to INH or RIF). INH resistance was the most common resistance pattern (36.5%) noted among patients and was significantly associated with new TB cases (69% vs. 31%; P=0.01). During TB treatment, 3/48 patients (6.3%) failed treatment and 11/48 (22.9%) died. Patients with MDR-TB were more likely to die during treatment (44.4% vs. 10%; P=0.011).

Conclusions: Any drug resistance in previously treated TB cases among HIV-infected patients remains high. The risk of death is increasing in MDR-TB/HIV co-infected patients.
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http://dx.doi.org/10.1016/j.jgar.2017.06.010DOI Listing
December 2017

HLA-B*1502 in Iranian Children with Anticonvulsant Drugs-Induced Skin Reactions.

Iran J Child Neurol 2017 ;11(2):26-30

Department of Immunology and Allergy, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Objective: Anticonvulsant drugs can cause various forms of skin drug reactions, ranging from exanthema to severe blistering reactions. An association between HLA-B*1502 allele and severe skin reactions have been reported.

Materials & Methods: Fifteen patients with severe skin reactions following treatment with anticonvulsant drugs (Carbamazepine, lamotrigine, phenobarbital, primidone) and 15 controls (age-matched epileptic patients taking similar anticonvulsants without drug eruption) were included. They were referred to Mofid Children's Hospital in Tehran, Iran, between Jan 2012 to Jan 2014. Genomic DNA was extracted from peripheral blood of all patients and HLA- B*1502 genotype was detected by real-time PCR.

Results: None of the patients was positive for HLA- B*1502, but two patients in control group had positive HLA- B*1502.

Conclusion: The HLA- B*1502 is not correlated with severe anticonvulsant drugs -induced skin reactions in Iranian children.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493826PMC
January 2017